Don't Blame The Egg...

Age-related Infertility may have less to do with eggs than the environment in which they live, suggesting a new route to IVF success.

Women become less fertile with age — that much we’ve known for a long time. But the fertility of women who are trying to conceive using in vitro fertilization (IVF) also declines dramatically after the age of 40 — and now researchers understand why.

It's not the eggs themselves that seem to be the problem, but rather it’s the “helper” cells that surround the eggs. The findings suggest that harvesting eggs earlier in the cycle rather than later may lead to greater IVF success.

The team looked at the eggs of women who were 21-29 and 30-37, as well as women aged 43-47 who were no longer fertile. The women in the oldest group had changes in their granulosa cells — the cells that surround the egg in the ovary and “tell” the ovaries what to do using hormone signals.

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Harvesting eggs earlier in the cycle rather than later may lead to greater IVF success.

In this group of older women, the granulosa cells had fewer receptors for follicle simulating hormone (FSH) which signals the egg to mature, and more receptors for progesterone and luteinizing hormone, which cue the ovaries not to get an egg ready for ovulation.

Normally, luteinizing hormone rises just after ovulation, so the ovary doesn’t ready a second egg too quickly; if it happens at other times, as in the older group of women, fertilization may simply not be possible.

“We used to think that aging eggs were responsible for poor IVF success rates in older women, but here we show that it is more due to the aging of the egg's environment,” study author Yanguang Wu said in a statement. “The chances of reversing damage to an egg are practically zero and so these findings are exciting because it's much more hopeful to therapeutically target the egg's supporting environment.”

The team reasoned that if they harvested eggs earlier in a woman's cycle, they might not be as subjected to the harmful hormone cues from the surrounding cells. So they tried harvesting when the follicle (the protective “padding” around the egg) was 16 mm in diameter rather than the usual 19-21 mm. And indeed, these eggs produced better quality embryos and better IVF success rates.

The discovery offers a new way of thinking about ovarian aging and could improve the results of fertility treatments, particularly in older women.

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Wu says more work will have to be done to test the findings in other groups of women. But in the meantime, doctors may want to take the results into consideration as they work with their IVF patients and families. In any case, it should give women and their doctors hope that fertilization rates may be improved in the future, with more healthy pregnancies to follow.

The study was carried out at The Centre for Human Reproduction in New York and published in the Journal of Endocrinology.